China's AIDS Treatment Program Reduces Deaths

Since its inception in 2002, China’s National Free Antiretroviral Treatment Program has substantially reduced death rates among thousands of adults with HIV/AIDS, scientists report in today’s issue of the Annals of Internal Medicine. The death rate during the first six months of treatment remains high, however, and treatment fails for approximately half of those who complete five years of antiretroviral therapy.

Ray Y. Chen, M.D., M.S.P.H., of the National Institute of Allergy and Infectious Diseases, part of the U.S. National Institutes of Health, co-authored the study with first author Fujie Zhang, M.D., of the Chinese Center for Disease Control and Prevention, and colleagues. The study evaluated more than 48,000 participants and marks the first report of outcomes to five years in a cohort of this size in a national HIV treatment program of a developing country.

Co-funded by the U.S. Centers for Disease Control and Prevention Global AIDS Program and the China Ministry of Health, the authors analyzed the Chinese HIV treatment program to assess mortality, treatment failure rates as determined by measures of immune function, and risk factors for these outcomes over five years among adults new to antiretroviral therapy.

To qualify for the free Chinese treatment program, an HIV-infected person must have one of three measures of immune dysfunction: fewer than 200 CD4+ T cells per microliter of blood, fewer than 1,200 white blood cells called lymphocytes per microliter, or severe HIV-related disease as defined by the World Health Organization (WHO). People who enrolled in the program received free highly active antiretroviral treatment (HAART) consisting of zidovudine or stavudine, lamivudine (which replaced didanosine in 2005), and nevirapine. If this treatment regimen failed, the authors reported, almost no access to second-line therapy was available during the study period.

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The scientists found that the death rate for participants in the Chinese program dropped from 22.6 deaths per 100 person-years when beginning treatment to between 4 and 5 deaths per 100 person-years after six months of HAART. This means that initially, for every 100 people who survived one year, 22.6 people died; after six months on treatment, however, only 4 to 5 people died for every 100 who survived one year. This lower AIDS mortality rate, comparable to rates in many low- and middle-income countries, remained steady over the subsequent 4.5 years, which the authors cite as a strength of the treatment program.

The study identified two risk factors associated with death among program participants: beginning treatment with fewer than 50 CD4+ T cells/microliter and beginning with four to five key symptoms associated with AIDS-related opportunistic infections—both signs of extreme immune dysfunction. These findings suggest that many HIV-infected individuals in the program begin treatment too late, the authors write. They recommend that China counteract this trend by expanding its HIV screening program to identify infected people earlier and by fighting HIV-related stigma and discrimination, which may deter some people from getting screened and accessing care.

A limitation the authors note was their inability to identify treatment failure by direct measurement of the amount of HIV in the blood—the gold standard. Instead, they determined treatment failure from measurements of CD4+ T cell counts, an indirect method recommended by the WHO for resource-limited settings because it is less expensive and more readily available.

The cumulative proportion of patients in the program for whom treatment failed increased from 12 percent at one year to approximately 50 percent at five years, the study found. Calling this trend “alarming,” the authors emphasize the need for viable second-line HAART regimens, which China introduced into the program in 2008. The treatment failure rate at one year is similar to rates reported by other developing countries, but there are no reports of five-year treatment failure rates from similar nations.

Now, the authors conclude, one of the Chinese program’s biggest challenges is determining how to scale up access to second-line treatment carefully so as to prevent further treatment failure and the need for third-line therapy.

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